SFRP4
protein-codingsecreted frizzled related protein 4, the group of Secreted frizzled-related proteins
Gene summary
Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~119.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009943
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0009943
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009943
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009943
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SFRP4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003014.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 42 | 2 | 45 | ||
| missense | 2 | 79 | 2 | 83 | ||
| nonsense | 5 | 5 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 7 | 1 | 8 | |||
| splice donor/acceptor (+/-2bp) | 2 | 1 | 3 | |||
| Total | 12 | 4 | 83 | 44 | 2 | 145 |
Highest pathogenic variant AF is 0.0000068409
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003005.2 | 6 | MANE Select | |
| Ensembl | ENSP00000410715.2 | 6 | MANE Select | |
| Ensembl | ENSP00000402262.2 | 5 | Standard | |
| Ensembl | ENSP00000551946.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Wnt signaling pathway - Homo sapiens (human)
- Adipogenesis
- Regulation of Wnt-B-catenin Signaling by Small Molecule Compounds
- Wnt Signaling Pathway
- Wnt Canonical
Biological Process
- positive regulation of receptor internalization
- negative regulation of cell population proliferation
- response to hormone
- positive regulation of gene expression
- cell differentiation
Molecular Function
- protein binding
- Wnt-protein binding
Cellular Component
- extracellular space
- nucleus
- cytoplasm
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000436072
- Coding exons
- 6
- Length
- 119755
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125748
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0459 | 210 | 212 | 0.991 | 0.0000114 | 2285 |
| Missense (PolyPhen) | 81 | 85.546 | 0.94686 | 965 | ||
| Synonymous | 0.188 | 75 | 77.1 | 0.973 | 0.00000418 | 646 |
| Loss of Function | 1.72 | 9 | 16.6 | 0.543 | 7.73e-7 | 180 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00074 | 0.00074 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927). {ECO:0000250|UniProtKB:Q9JLS4, ECO:0000250|UniProtKB:Q9Z1N6, ECO:0000269|PubMed:12952927}.;
- Disease
- DISEASE: Pyle disease (PYL) [MIM:265900]: A disorder characterized by cortical-bone thinning, limb deformity, bone fragility and fractures. {ECO:0000269|PubMed:27355534}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.254
Intolerance Scores
- LoFtool
- 0.642
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.99
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.121
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |